Interplay between aggression, brain monoamines and fur color mutation in the American mink.

Domestication of wild animals alters the aggression towards humans, brain monoamines and coat pigmentation. Our aim is the interplay between aggression, brain monoamines and depigmentation. The Hedlund white mutation in the American mink is an extreme case of depigmentation observed in domesticated animals. The aggressive (-2.06 ± 0.03) and tame (+3.5 ± 0.1) populations of wild-type dark brown color (standard) minks were bred during 17 successive generations for aggressive or tame reaction towards humans, respectively. The Hedlund mutation was transferred to the aggressive and tame backgrounds to generate aggressive (-1.2 ± 0.1) and tame (+3.0 ± 0.2) Hedlund minks. Four groups of 10 males with equal expression of aggressive (-2) or tame (+5) behavior, standard or with the Hedlund mutation, were selected to study biogenic amines in the brain. Decreased levels of noradrenaline in the hypothalamus, but increased concentrations of the serotonin metabolite, 5-hydroxyindoleacetic acid and dopamine metabolite, homovanillic acid, in the striatum were measured in the tame compared with the aggressive standard minks. The Hedlund mutation increased noradrenaline level in the hypothalamus and substantia nigra, serotonin level in the substantia nigra and striatum and decreased dopamine concentration in the hypothalamus and striatum. Significant interaction effects were found between the Hedlund mutation and aggressive behavior on serotonin metabolism in the substantia nigra (P < 0.001), dopamine level in the midbrain (P < 0.01) and its metabolism in the striatum (P < 0.05). These results provide the first experimental evidence of the interplay between aggression, brain monoamines and the Hedlund mutation in the American minks.

The cortisol response to ACTH in pigs, heritability and influence of corticosteroid-binding globulin.

In the search for biological basis of robustness, this study aimed (i) at the determination of the heritability of the cortisol response to ACTH in juvenile pigs, using restricted maximum likelihood methodology applied to a multiple trait animal model, and (ii) at the study of the relationships between basal and stimulated cortisol levels with corticosteroid-binding globulin (CBG), IGF-I and haptoglobin, all important players in glucose metabolism and production traits. At 6 weeks of age, 298 intact male and female piglets from 30 litters (30 dams and 30 boars) were injected with 250 µg ACTH(1-24) (Synacthen). Blood was taken before ACTH injection to measure basal levels of cortisol, glucose, CBG, IGF-I and haptoglobin, and 60 min later to measure stimulated cortisol levels and glucose. Cortisol increased 2.8-fold after ACTH injection, with a high correlation between basal and stimulated levels (phenotypic correlation, r p=0.539; genetic correlation, r g=0.938). Post-ACTH cortisol levels were highly heritable (h 2=0.684) and could therefore be used for genetic selection of animals with a more reactive hypothalamic-pituitary-adrenocortical axis. CBG binding capacity correlated with cortisol levels measured in basal conditions in males only. No correlation was found between CBG binding capacity and post-ACTH cortisol levels. Basal IGF-I concentration was positively correlated with BW at birth and weaning, and showed a high correlation with CBG binding capacity with a strong sexual dimorphism, the correlation being much higher in males than in females. Basal haptoglobin concentrations were negatively correlated with CBG binding capacity and IGF-I concentrations. Complex relationships were also found between circulating glucose levels and these different variables that have been shown to be related to glucose resistance in humans. These data are therefore valuable for the genetic selection of animals to explore the consequences on production and robustness traits, but also point at pigs as a relevant model to explore the underlying mechanisms of the metabolic syndrome including the contribution of genetic factors.

Association study of molecular polymorphisms in candidate genes related to stress responses with production and meat quality traits in pigs.

The hypothalamic-pituitary-adrenal (HPA) axis exerts a large range of effects on metabolism, the immune system, inflammatory processes, and brain functions. Together with the sympathetic nervous system, it is also the most important stress-responsive neuroendocrine system. Both systems influence production traits, carcass composition, and meat quality. The HPA axis may be a critical target for genetic selection of more robust animals. Indeed, numerous studies in various species have demonstrated the importance of genetic factors in shaping the individual HPA axis phenotype, and genetic polymorphism can be found at each level of the axis, including hormone production by the adrenal cortices under stimulation by adrenocorticotropic hormone (ACTH), hormone bioavailability, or receptor and postreceptor mechanisms. The aim of the present experiment was to extend these findings to the brain neurochemical systems involved in stress responses. To this end, a number of candidate genes were sequenced for molecular polymorphisms and their association was studied with stress neuroendocrine and production traits in a genetically diverse population consisting of 100 female pigs from an advanced intercross (F10-F12) between 2 highly divergent breeds, Large White (LW) and Meishan (MS). The LW breed has a high production potential for lean meat and a low HPA axis activity, and the MS breed has low growth rate, fat carcasses-but large litters of highly viable piglets-and a high HPA axis activity. Candidate genes were chosen in the catecholaminergic and serotonergic pathways, in the pituitary control of cortisol production, among genes previously demonstrated to be differentially expressed in ACTH-stimulated adrenal glands from LW and MS pigs, and in cortisol receptors. Sixty new polymorphisms were found. The association study with carcass and meat quality traits and with endocrine traits showed a number of significant results, such as monoamine oxidase (MAOA) polymorphisms with growth rate (P = 0.01); lean content and intramuscular fat (P < 0.01), which are the most important traits for carcass value; dopamine receptor D3 (DRD3) with carcass composition (P < 0.05); and vasopressin receptor 1B (AVPR1B) with meat quality traits (P ≤ 0.05). The effect of these polymorphisms on neuroendocrine parameters (eg DRD3 and HPA axis or AVPR1B and catecholamines) indicates information regarding their biological mechanism of action.

Molecular genetics of the adrenocortical axis and breeding for robustness.

The concept of robustness refers to the combination of a high production potential and a low sensitivity to environmental perturbations. The importance of robustness-related traits in breeding objectives is progressively increasing toward the production of animals with a high production level in a wide range of climatic conditions and production systems, together with a high level of animal welfare. Current strategies to increase robustness include selection for "functional traits," such as skeletal and cardiovascular integrity, disease resistance, and mortality at various stages. It is also possible to use global evaluation of sensitivity to the environment (eg reaction norm analysis or canalization), but these techniques are difficult to implement in practice. The glucocorticoid hormones released by the adrenal cortex exert a wide range of effects on metabolism, the cardiovascular system, inflammatory processes, and brain function, for example. Protein catabolism toward energy production and storage (lipids and glycogen) supports their pivotal role in stress responses aiming at the adaptation and survival of individuals under strong environmental pressure. Large individual variations have been described in adrenocortical axis activity, with important physiopathological consequences. In terms of animal production, higher cortisol levels have negative effects on growth rate and feed efficiency and increase the fat:lean ratio of carcasses. On the contrary, cortisol has positive effects on functional traits and adaptation. Intense selection for lean tissue growth and more generally high protein output during the past decades has concomitantly reduced cortisol production, which may be responsible for the negative effects of selection on functional traits. In this paper, we review experimental evidence suggesting that the balance between production and functional traits was modified in favor of improved robustness by selecting animals with higher adrenocortical axis activity, as well as the molecular genetic tools that can be used to fine-tune this objective.

A pharmacological evidence of positive association between mouse intermale aggression and brain serotonin metabolism.

The neurotransmitter serotonin (5-HT) is involved in the regulation of mouse intermale aggression. Previously, it was shown that intensity of mouse intermale aggression was positively associated with activity of the key enzyme of 5-HT synthesis - tryptophan hydroxylase 2 (TPH2) in mouse brain. The aim of the present study was to investigate the effect of pharmacological activation or inhibition of 5-HT synthesis in the brain on intermale aggression in two mouse strains differing in the TPH2 activity: C57BL/6J (B6, high TPH2 activity, high aggressiveness) and CC57BR/Mv (BR, low TPH2 activity, low aggressiveness). Administration of 5-HT precursor L-tryptophan (300 mg/kg, i.p.) to BR mice significantly increased the 5-HT and 5-hydroxyindoleacetic acid (5-HIAA) levels in the midbrain as well as the number of attacks and their duration in the resident-intruder test. And vice versa, administration of TPH2 inhibitor p-chlorophenylalanine (pCPA) (300 mg/kg, i.p., for 3 consecutive days) to B6 mice dramatically reduced the 5-HT and 5-HIAA contents in brain structures and attenuated the frequency and the duration of aggressive attacks. At the same time, L-tryptophan or pCPA did not influence the percentage of aggressive mice and the attack latency reflecting the threshold of aggressive reaction. This result indicated that the intensity of intermale aggression, but not the threshold of aggressive reaction is positively dependent on 5-HT metabolism in mouse brain.

Breeding for robustness: the role of cortisol.

Robustness in farm animals was defined by Knap as 'the ability to combine a high production potential with resilience to stressors, allowing for unproblematic expression of a high production potential in a wide variety of environmental conditions'. The importance of robustness-related traits in breeding objectives is progressively increasing towards the production of animals with a high production level in a wide range of climatic conditions and production systems, together with a high level of animal welfare. Current strategies to increase robustness include selection for 'functional traits', such as skeletal and cardiovascular integrity, disease resistance and mortality in various stages. It is also possible to use global evaluation of sensitivity to the environment (e.g. reaction norm analysis or canalization), but these techniques are difficult to implement in practice. The hypothalamic-pituitary-adrenocortical (HPA) axis is the most important stress-responsive neuroendocrine system. Cortisol (or corticosterone) released by the adrenal cortices exerts a large range of effects on metabolism, the immune system, inflammatory processes and brain function, for example. Large individual variations have been described in the HPA axis activity with important physiopathological consequences. In terms of animal production, higher cortisol levels have negative effects on growth rate and feed efficiency and increase the fat/lean ratio of carcasses. On the contrary, cortisol has positive effects on traits related to robustness and adaptation. For instance, newborn survival was shown to be directly related to plasma cortisol levels at birth, resistance to bacteria and parasites are increased in animals selected for a higher HPA axis response to stress, and tolerance to heat stress is better in those animals that are able to mount a strong stress response. Intense selection for lean tissue growth during the last decades has concomitantly reduced cortisol production, which may be responsible for the negative effects of selection on piglet survival. One strategy to improve robustness is to select animals with higher HPA axis activity. Several sources of genetic polymorphism have been described in the HPA axis. Hormone production by the adrenal cortices under stimulation by adrenocorticotropin hormone is a major source of individual differences. Several candidate genes have been identified by genomic studies and are currently under investigation. Bioavailability of hormones as well as receptor and post-receptor mechanisms are also subject to individual variation. Integration of these different sources of genetic variability will allow the development of a model for marker-assisted selection to improve animal robustness without negative side effects on production traits.

Effect of selective agonist of serotonin 5-HT1A receptors on defensive behavior in mice with different predisposition to catalepsy.

We studied the effect of activation of serotonin 5-HT1A receptors with selective agonist 8-OH-DPAT (0.1, 0.5, and 1.0 mg/kg) on intraspecies aggression and freezing reaction (catalepsy) in male mice of catalepsy-resistant AKR/J and two catalepsy-prone strains CBA/Lac and congenic AKR.CBA-D13Mit76. The latter strain differs from AKR strain only by terminal chromosome 13 fragment transferred from CBA strain and containing a locus determining predisposition to catalepsy and a gene encoding 5-HT1A receptor. 8-OH-DPAT in a low dose (0.1 mg/kg) affecting primarily presynaptic receptors suppressed aggressive behavior in CBA mice, but had no effect on the time of cataleptic freezing. At the same time, this dose of the drug produced no significant effect on aggression in AKR and AKR.CBA-D13Mit76 mice, but significantly attenuated freezing in AKR.CBA-D13Mit76 mice. High doses of 8-OH-DPAT (0.5 and 1 mg/kg) which affected mainly postsynaptic receptors inhibited catalepsy in CBA and AKR.CBA-D13Mit76 mice and in a dose of 1 mg/kg it suppressed aggression in all tested mouse strains. We concluded that the genome of the recipient strain (AKR) modulated the involvement of 5-HT(1A) receptors into the regulation of aggression and catalepsy in mice.

Marker-assisted dissection of genetic influences on motor and neuroendocrine sensitization to cocaine in rats.

This study investigated genetic influences on behavioral and neuroendocrine responses to cocaine sensitization. We used male and female rats of the inbred strains Lewis (LEW) and spontaneously hypertensive rats (SHR), which display genetic differences in stress-related responses. The influence of two quantitative trait loci (QTL; Ofil1 and Ofil2 on chromosomes 4 and 7), which modulate stress reactivity in rats, on the effects of cocaine was also investigated through the use of recombinant lines (derived from a LEW x SHR intercross) selected by their genotype at Ofil1 and Ofil2. Animals were given repeated cocaine or saline injections and tested for locomotion (induction of sensitization). Two weeks later, all animals were challenged with cocaine, and locomotion and corticosterone levels were measured (expression of sensitization). Results indicated that male SHR rats showed more behavioral sensitization than LEW rats, whereas no strain differences in sensitization were seen among females. When challenged with cocaine, LEW and SHR rats of both sexes pretreated with cocaine showed behavioral sensitization compared with saline pretreated animals; however, only LEW rats displayed an increase in the corticosterone levels. Ofil1 was found to influence the induction of sensitization in males and Ofil2 modulated the locomotor effect of cocaine in females. This study provides evidence of a genotype-dependent relationship between the induction and expression of cocaine sensitization, and between the behavioral and neuroendocrine responses induced by cocaine. Moreover, the Ofil1 and Ofil2 loci may contain one or more genes that control the behavioral effects of cocaine in rats.

[A new yeast species Candida anutae sp.nov. from the fruiting bodies of agaricus]. / Novyi vid drozhzhei Candida anutae sp.nov. iz plodovykh tel agarikovykh gribov.

Among the yeasts isolated from the fruiting bodies of different species of agarics picked in forests near Moscow and Turku (Finland) in 1995-1998, populations of an earlier unknown species, morphologically similar to Metschnikowia lunata but differing from it by physiological characteristics and the absence of asci with spores, were constantly found. Description of the new species is given within the genus Candida Berkhout.